Probing the Aglycon Promiscuity of an Engineered Glycosyltransferase

Authors

  • Richard W. Gantt,

    1. UW National Cooperative Drug Discovery Group, Laboratory for Biosynthetic Chemistry, School of Pharmacy, University of Wisconsin-Madison, 777 Highland Avenue, Madison, WI 53705 (USA), Fax: (+1) 608-262-5345
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  • Randal D. Goff,

    1. UW National Cooperative Drug Discovery Group, Laboratory for Biosynthetic Chemistry, School of Pharmacy, University of Wisconsin-Madison, 777 Highland Avenue, Madison, WI 53705 (USA), Fax: (+1) 608-262-5345
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  • Gavin J. Williams,

    1. UW National Cooperative Drug Discovery Group, Laboratory for Biosynthetic Chemistry, School of Pharmacy, University of Wisconsin-Madison, 777 Highland Avenue, Madison, WI 53705 (USA), Fax: (+1) 608-262-5345
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  • Jon S. Thorson Prof.

    1. UW National Cooperative Drug Discovery Group, Laboratory for Biosynthetic Chemistry, School of Pharmacy, University of Wisconsin-Madison, 777 Highland Avenue, Madison, WI 53705 (USA), Fax: (+1) 608-262-5345
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  • The authors thank the University of Wisconsin-Madison School of Pharmacy Analytical Facility for analytical support. This research was supported in part by National Institutes of Health Grants AI52218 and U19 CA113297.

Abstract

original image

A sweet library: Two variants (wild-type (WT) and a triple mutant) of glycosyltransferase (GT) OleD have been shown to catalyze glycosylation of over 70 substrates, formation of O-, S- and N-glycosidic bonds, and iterative glycosylation (see scheme). Identified substrates include nucleophiles not previously known to act in GT reactions and span numerous natural product and therapeutic drug classes.

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